NogoA inhibits neurite outgrowth of motoneurons (NOM) through interaction Match Holder with its receptors, Nogo66/NgR.Inhibition of Nogo receptors rescues NOM, but not to the extent exhibited by NogoA-knockout mice, suggesting the presence of other pathways.We found that NogoA-overexpressing muscle cells reduced phosphoglycerate kinase 1 (Pgk1) secretion, resulting in inhibiting NOM.
Apart from its glycolytic role and independent of the Nogo66 pathway, extracellular Pgk1 stimulated Bottle Sleeves NOM by triggering a reduction of p-Cofilin-S3, a growth cone collapse marker, through decreasing a novel Rac1-GTP/p-Pak1-T423/p-P38-T180/p-MK2-T334/p-Limk1-S323/p-Cofilin-S3 molecular pathway.Not only did supplementary Pgk1 enhance NOM in defective cells, but injection of Pgk1 rescued denervation in muscle-specific NogoA-overexpression of zebrafish and an Amyotrophic Lateral Sclerosis mouse model, SOD1 G93A.Thus, Pgk1 secreted from muscle is detrimental to motoneuron neurite outgrowth and maintenance.